ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Transcatheter arterial embolization (TAE) is the mainstay for treating advanced hepatocellular carcinoma (HCC), and the performance of the embolization material is crucial in TAE. With the development of medical imaging and the birth of "X-ray-free" technologies, we designed a new dual-mode imaging material of dimethoxy tetraphenyl ethylene (DMTPE) via emulsification by mixing poly(N-isopropylacrylamide-co-acrylic acid) (PNA) with lipiodol and fluorocarbons, which was evaluated for temperature sensitivity, stability, and dual-mode visualization in vitro. Additionally, blood vessel casting embolization and renal artery imaging were assessed in healthy rabbits. In a rabbit model with a VX2 tumor, the effectiveness of TAE for treating HCC was examined, with an emphasis on evaluating long-term outcomes of embolization and its effects on tumor growth, necrosis, and proliferation through imaging techniques. In vitro experiments confirmed that the temperature-sensitive dual-oil-phase Pickering emulsion had good flow, stable contrast, and embolism when the oil-to-oil ratio and water-to-oil ratio were both 7:3 ( v/v) and stabilized with 8% PNA. Similarly, in vivo, arterial embolization confirmed the excellent properties of DMTPE prepared at the abovementioned ratios. It was observed that DMTPE not only has an antitumor effect but can also achieve dual imaging using X-rays and ultrasound, making it a promising excellent vascular embolization material for TAE in tumor treatment.

Transcatheter arterial embolization(TAE)is the mainstay for treating advanced hepatocellular carcinoma(HCC),and the performance of the embolization material is crucial in TAE.With the development of medical imaging and the birth of"X-ray-free"technologies,we designed a new dual-mode imaging material of dimethoxy tetraphenyl ethylene(DMTPE)via emulsification by mixing poly(N-iso-propylacrylamide-co-acrylic acid)(PNA)with lipiodol and fluorocarbons,which was evaluated for temperature sensitivity,stability,and dual-mode visualization in vitro.Additionally,blood vessel casting embolization and renal artery imaging were assessed in healthy rabbits.In a rabbit model with a VX2 tumor,the effectiveness of TAE for treating HCC was examined,with an emphasis on evaluating long-term outcomes of embolization and its effects on tumor growth,necrosis,and proliferation through imaging techniques.In vitro experiments confirmed that the temperature-sensitive dual-oil-phase Pickering emulsion had good flow,stable contrast,and embolism when the oil-to-oil ratio and water-to-oil ratio were both 7∶3(v/v)and stabilized with 8％PNA.Similarly,in vivo,arterial embolization confirmed the excellent properties of DMTPE prepared at the abovementioned ratios.It was observed that DMTPE not only has an antitumor effect but can also achieve dual imaging using X-rays and ultrasound,making it a promising excellent vascular embolization material for TAE in tumor treatment.

Objective:To analyze the spatial-temporal epidemiological characteristics of pertussis from 2013 to 2022 in Hebei Province and to provide a reference for improving prevention and control measures.Methods:Based on the data of pertussis reported in Hebei Province during 2013-2022 to analyze the popular characteristic, the ArcGIS 10.8 software was used to construct a ring map and to perform spatial autocorrelation analysis; the SaTScan 10.1 software was used for spatial-temporal scan statistics.Results:There were 6 715 cases of the cumulative report in Hebei Province from 2013 to 2022 without death. The annual report incidence was 0.90/100 000. The overall incidence rate showed an upward trend from 2013 to 2019, and during 2020-2021, it showed a sharp decline, but in 2022, it showed a sharp increase. Summer and autumn are the peak seasons of the epidemic. The incidence was highest in age group <1 year (48.67%), and the lowest age group in age group ≥15 years (0.45%) and mainly scattered children (78.03%); the incidence about men is higher than women. Spatial autocorrelation analysis showed that the onset of pertussis has spatial clustering, and high-high clusters were found in Langfang, Baoding, and Cangzhou, the top three countries with reported incidence. The area covered by a low-low cluster was consistent with the distribution of the corresponding low-incidence areas in this study. Space-time scan detects five statistically significant areas, and three zones were concentrated in 2022.Conclusions:The incidence of pertussis in Hebei had obvious season, population, and area-specific differences. There was obvious spatiotemporal and clustering, so the control of key areas should target the characteristics of time and space.

Purpose To detect the expression of peroxiso-mal membrane protein 4(PXMP4)in breast cancer tissues and to explore the effect of PXMP4 on the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of breast cancer cells.Methods Bioinformatics and immunohistochemistry(IHC)were used to detect the expression of PXMP4 in breast cancer tissues.In breast cancer cells,Western blot was used to detect the expression of Cyclin D1,E-cadherin,vimentin and N-cadherin after knockdown and overexpression of PMXP4.The proliferation ability of breast cancer cells was analyzed by CCK-8 and plate cloning assay.Scratch healing and Transwell assay an-alyzed the migration and invasion ability of breast cancer cells.Lentivirus was used to construct a PXMP4-silenced MCF-7 cell line,and the PXMP4-silenced MCF-7 cells were injected into the subcutaneous or tail vein of mice to observe lung metastasis and the number of subcutaneous tumors.Results Bioinformat-ics and IHC showed that the expression of PXMP4 in breast cancer tissues was significantly increased(P＜0.05),and the prognosis of breast cancer patients with high expression of PXMP4 was poor(P＜0.05).The clinicopathological analysis showed that the expression of PXMP4 was correlated with tumor grade and lymph node metastasis(P＜0.05).In vitro knock-down of PMXP4 inhibited the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).Conversely,overex-pression of PXMP4 promoted the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).In vivo,the number of lung metastases,the size of subcutaneous tumor,and the expression of Ki67 in tumor tissue were significantly de-creased after silenced PXMP4(P＜0.05).Conclusion PXMP4 is related to tumor grading and lymph node metastasis.PXMP4 promotes proliferation,invasion and EMT process of breast cancer cells.

Objective:To investigate the value of diffusion kurtosis imaging (DKI) combined with quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting axillary lymph node metastasis in breast cancer.Methods:A total of 150 cases of breast cancer confirmed by pathology in the Affiliated Hospital of Jining Medical University were retrospectively analyzed. 68 cases had axillary lymph node (ALN) metastasis and 82 cases had no ALN metastasis. All breast lesions were examined by DKI and DCE-MRI before operation. We analyzed clinical case data, routine MRI features, DKI, and DCE-MRI parameters between two groups, including diffusion kurtosis (MK), mean diffusion rate (MD), volume transfer constant (K trans), extravascular volume fraction (Ve), and rate constant (Kep); The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of quantitative parameters for ALN metastasis of breast cancer. Results:The proportion of lesions with blurred edges in the metastatic group was higher than that in the non ALN metastatic group ( P=0.032); The proportion of uneven and circular enhancement within the ALN metastasis group was relatively high ( P=0.018). The MD value of the ALN transfer group was lower than that of the group without ALN transfer ( P=0.021); The MK value, K trans value, and Kep value were higher than those in the group without ALN metastasis (all P<0.01). The K trans value of DCE-MRI model was the most effective in diagnosing ALN metastasis of breast cancer, and the area under the ROC curve (AUC) was 0.831; The AUC of DCE-MRI model was 0.833, which was higher than that of DKI model (AUC=0.733), and the difference was statistically significant ( Z=2.208; P=0.027). The AUC of DCE-MRI and DKI models were higher than that of conventional MRI models ( Z=3.184, P=0.002; Z=1.917, P=0.046). The sensitivity and accuracy of combined DKI and DCE-MRI models in the diagnosis of ALN metastasis in breast cancer were higher than those of single model. Conclusions:DKI and DCE-MRI models can be used to predict axillary lymph node metastasis in breast cancer. Among them, the K trans value of DCE-MRI model is the most effective in diagnosing axillary lymph node metastasis in breast cancer.

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.